Adaptation to Fluconazole Via Aneuploidy Enables Cross‐Adaptation to Amphotericin B and Flucytosine in Cryptococcus Neoformans
Open accessAbstract
Cryptococcosis is a globally distributed invasive fungal infection caused by infections with Cryptococcus neoformans or Cryptococcus gattii . Only three classes of therapeutic drugs are clinically available for treating cryptococcosis: polyenes (amphotericin B), azoles (fluconazole), and pyrimidine analogues (flucytosine).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Exposure to fluconazole at subinhibitory concentrations for 48 h may cause C. neoformans to acquire different aneuploid chromosomes that confer heteroresistance to fluconazole and cross-resistance to 5-FC.
“Yang et al. found that exposure to fluconazole at subinhibitory concentrations for a short period of time (48 h) may cause C. neoformans to acquire different aneuploid chromosomes that confer heteroresistance to fluconazole and cross-resistance to 5-FC [153].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [153]
The Results section (“Effect of short-time exposure to sub-MIC of fluconazole on adaptation”; page unavailable) reports aneuploid adaptors after 48 hours at a subinhibitory fluconazole concentration. The Introduction and Discussion say that some karyotypes conferred fluconazole heteroresistance and 5-FC cross-tolerance, not 5-FC cross-resistance; the paper explicitly distinguishes tolerance from resistance. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDespite initial susceptibility to drug, heteroresistant subpopulations can expand during therapy, partially due to antifungal exposure, characterized as emergence of resistance-related genetic mutations, and clinically as relapse or progression of infection.
“Despite initial susceptibility to the drug, heteroresistant subpopulations can expand during therapy, partially due to antifungal exposure, characterized as the emergence of resistance-related genetic mutations, and clinically as relapse or progression of the infection [110,151,152,153].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [153]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredHeteroresistant subpopulations may exist at low frequencies or exhibit resistance only under specific conditions, such as prolonged exposure to antifungal agents or within certain host environments.
“This limitation arises because heteroresistant subpopulations may exist at low frequencies or exhibit resistance only under specific conditions, such as prolonged exposure to antifungal agents or within certain host environments [153,165,167,168].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [153]
The Results section reports that six of 120 colonies showed increased growth after fluconazole exposure, supporting the possibility of a low-frequency subpopulation. The Introduction and Discussion describe drug-dependent heteroresistance, but emphasize that even short exposure was sufficient; the paper does not establish that prolonged exposure or particular host environments are required for resistance to appear. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe primary HR mechanism in C. glabrata distinguishes itself from models in C. albicans and C. neoformans, where aneuploidy is a common driver.
“Mechanistically, the primary HR mechanism in C. glabrata distinguishes itself from models in C. albicans and C. neoformans, where aneuploidy is a common driver [27, 42, 43].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [42]
Exposure of C. parapsilosis to tunicamycin did not reveal any relationship between aneuploidy and heteroresistance.
“However, unlike C. neoformans, exposure of C. parapsilosis to tunicamycin did not reveal any relationship between aneuploidy and heteroresistance [3,153].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [153]
The Introduction and Discussion describe aneuploidy and fluconazole heteroresistance in C. neoformans, not tunicamycin exposure in C. parapsilosis. Searches for “tunicamycin” and “C. parapsilosis” found no passage addressing the attributed finding in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 28 · Cited by 49
Research works printed but not linked: 1
- [10]WHO. 2018. Guidelines for the diagnosis, prevention and management of cryptococcal disease in hiv-infected adults, adolescents and children: supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. WHO, Geneva, Switzerland. 30285342
- Authors
- Yang, F., Gritsenko, V., Lu, H., Zhen, C., Gao, L., Berman, J., & Jiang, Y.-Y.
- Affiliations
- Tongji University (CN)
- Tel Aviv University (IL)
- Department of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
- Corresponding author
- Berman, Judith
- Venue
- Microbiology Spectrum
- Publisher
- American Society for Microbiology
- Published
- 2021-10-31
- Volume
- 9
- Issue
- 2
- Pages
- e0072321-e0072321
- ISSN
- 2165-0497 (ISSN-L)
- PMC
- PMC8557924
- OpenAlex
- W3204680979
- Cited by
- 49
- References
- 28
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 9 · 2023: 11 · 2022: 6
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Microbiology Spectrum (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Israel Science Foundation (997/18)
- National Natural Science Foundation of China (82020108032)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Cryptococcus neoformans, aneuploidy, drug tolerance, cross-tolerance, amphotericin B, 5-fluorocytosine, antifungal resistance, cryptococcosis, minimum inhibitory concentration
- MeSH terms
- Adaptation, Physiological, Amphotericin B, Aneuploidy, Antifungal Agents, Cryptococcosis, Cryptococcus neoformans, Flucytosine, Humans, Microbial Sensitivity Tests, Fluconazole, Drug Resistance, Fungal, Cryptococcus gattii, Serogroup
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
